The overall objective of this research project is to study the molecular mechanisms involved in the adherence of bacteria to mucosal surfaces. We will focus on studies to identify the bacterial substances as well as the host substance involved in the binding process. Our studies have already shown that lipoteichoic acid (LTA) which binds spontaneously to various mammalian cell membranes is exposed on the surface of streptococci and serves to bind the organisms to human oral epithelial cells. We are now attempting to identify the membrane receptor site(s) for LTA and streptococcal binding. In another aspect of our studies we have recently shown that E. coli bind via mannose-like receptors in the membranes of epithelial cells. Temperature-sensitive mutant strains lose their pili and their ability to bind when grown at restrictive temperature but regain pili and ability to adhere at permissive temperature. We have obtained evidence, however, that certain nonpiliated strains adhere to epithelial cell via their outer membranes. It is hoped that the identification of the specific binding substances both on the bacteria and on the surface of epithelial cells will enable us to intervene in the infectious process at an early step before bacteria invade and produce tissue damage in the susceptible host.